title: Simvastatin alters fibroblastic cell responses involved in tissue repair.
abstract: OBJECTIVE
  Statins have been used to control hypercholesterolemia. However, these drugs also exert pleiotropic effects that include the modulation of inflammation and cell signaling. The present study has analyzed the effects of simvastatin on several cell responses involved in tissue repair, including cell adhesion, cell migration and invasion, actin cytoskeleton remodeling and cell viability.
  
  
  METHODS
  Primary cultures of gingival fibroblasts were stimulated with simvastatin. Cell adhesion was evaluated using a colorimetric assay. Cell spreading was evaluated microscopically. Cell migration and invasion were assessed using a scratch wound-healing assay and a bicameral cell culture system, respectively. Changes in actin cytoskeleton and focal adhesion assembly were evaluated through immunofluorescence for actin, vinculin and active β1 integrin. Rac activation was evaluated by means of a pull-down assay. Cell viability was assessed using a colorimetric assay that determines mitochondrial functionality. Data analysis was performed using the Mann-Whitney U-test.
  
  
  RESULTS
  Simvastatin diminished cell adhesion and spreading over a fibronectin matrix. It also altered the closure of scratch wounds induced on cell monolayers and cell invasion through a Transwell system. Simvastatin-treated cells displayed an altered lamellipodia with poorly developed focal adhesion contacts and reduced levels of β1 integrin activation. During cell spreading, simvastatin diminished Rac activation.
  
  
  CONCLUSIONS
  The present study shows that simvastatin may alter cell migration by disrupting the cell signaling networks that regulate the actin cytoskeleton dynamics. This mechanism may affect the response of gingival mesenchymal cells during wound healing.
authors.affiliation: Laboratory of Periodontal Physiology, Dentistry Academic Unit, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Cáceres
authors.forename: A
authors.initials: A
authors.lastname: Romero
authors.forename: M
authors.initials: M
authors.lastname: Copaja
authors.forename: G
authors.initials: G
authors.lastname: Díaz-Araya
authors.forename: J
authors.initials: J
authors.lastname: Martínez
authors.forename: P C
authors.initials: PC
authors.lastname: Smith
mesh_terms: D000199:Actins / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D019012:Integrin beta1 / Q000032:analysis; D008297:Male; D011554:Pseudopodia / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*; D016596:Vinculin / Q000032:analysis; D055815:Young Adult; D020744:rac GTP-Binding Proteins / Q000032:analysis
chemical_list: D000199:Actins; D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019012:Integrin beta1; D016596:Vinculin; D019821:Simvastatin; D020744:rac GTP-Binding Proteins